2013 Rustbelt RNA Meeting
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Poster number 58 submitted by Jun Jiang

Pseudouridine modifications modulate the folding of helix 69 and its response to environmental changes

Jun Jiang (Department of Chemistry, Wayne State University, Detroit, MI 48202), John SantaLucia, Jr. (Department of Chemistry, Wayne State University, Detroit, MI 48202), Christine S. Chow (Department of Chemistry, Wayne State University, Detroit, MI 48202)

Abstract:
Helix 69 (H69), a 19-nucleotide segment located within domain IV of the 23S ribosomal RNA, is a key component of the intersubunit bridge B2a in ribosomes. The sequence and secondary structure of H69 are highly conserved in each domain of life and throughout the phylogeny. An additional feature of conservation of H69 is a cluster of pseudouridine (Ψ) modifications within the loop region. NMR studies on oligonucleotides with and without Ψs have shown that these modifications reshape and influence the dynamic behavior of the H69 loop region. This structure modulation by Ψ modification is proposed to be correlated with a growth advantage of wild-type strains and conservation of Ψs. Meanwhile, it has been reported that H69 plays important structural and functional roles by displaying conformational adaptability, involving association with different factors such as Mg2+. The folding of H69 is also susceptible to environmental pH changes. NMR studies on H69 oligonucleotides with and without Ψ modifications suggest that the pseudouridylated H69 is more sensitive to environmental pH change than the unmodified construct, and reveal at least two Mg2+ binding sites. Thus, incorporation of environmental changes in the NMR studies enriches our understanding of the roles of Ψ in H69 structure and conformational behavior, and extends our knowledge towards the structures in physiological conditions. The results of these model studies are useful in research and development of antibiotic candidates that target H69.

References:
Jiang, J., Sakakibara, Y., Chow, C.S. (2013) Israel Journal of Chemistry 53: 379-390.
Goddard, N.L., Bonnet, G., Krichevsky, O. and Libchaber, A. (2000) Physical review letters 85: 2400-2403.
Sakakibara, Y., Abeysirigunawardena, S.C., Duc, A-C.E., Dremann, D.N., Chow, C.S. (2012) Angewandte Chemie International Edition 51: 12095-12098.
Blaha, G., Stanley, R.E., Steitz, T.A. (2009) Science 325: 966-970.
Klinge, S., Voigts-Hoffmann, F., Leibundgut, M., Arpagaus, S., Ban, N. (2011) Science 334: 941.

Keywords: pseudouridylation, pH, magnesium